Overall Incidence Of Colorectal Cancer Research Articles

Molecular Landscape and Therapeutic Strategies against Colorectal Cancer.

Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide. Although the overall incidence of CRC is decreasing, the incidence of young-onset CRC, characterized by a diagnosis of CRC before age 50, is increasing. Outcomes for CRC patients are improving, partly due to comprehensive molecular characterization of tumors and novel therapeutic strategies. Advances in genomic and transcriptomic analyses using blood- and tumor-tissue-based sequencing have facilitated identification of distinct tumor subtypes harboring unique biological characteristics and therapeutic vulnerabilities. These insights have led to the development and incorporation of targeted therapies and immunotherapy in CRC treatment. In this review, we discuss the molecular landscape and key oncogenes/tumor suppressors contributing to CRC tumorigenesis, metastasis, and therapeutic resistance. We also discuss personalized therapeutic strategies for subsets of CRC patients and provide an overview of evolving novel treatments being evaluated in clinical trials.

A Perspective Review on Diet Quality, Excess Adiposity, and Chronic Psychosocial Stress and Implications for Early-Onset Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer worldwide. Although the overall incidence of CRC has been decreasing over the past 40 y, early-onset colorectal cancer (EOCRC), which is defined as a CRC diagnosis in patients aged >50 y has increased. In this Perspective, we highlight and summarize the association between diet quality and excess adiposity, and EOCRC. We also explore chronic psychosocial stress (CPS), a less investigated modifiable risk factor, and EOCRC. We were able to show that a poor-quality diet, characterized by a high intake of sugary beverages and a Western diet pattern (high intake of red and processed meats, refined grains, and foods with added sugars) can promote risk factors associated with EOCRC development, such as an imbalance in the composition and function of the gut microbiome, presence of chronic inflammation, and insulin resistance. Excess adiposity, particularly obesity onset in early adulthood, is a likely contributor of EOCRC. Although the research is sparse examining CPS and CRC/EOCRC, we describe likely pathways linking CPS to tumorigenesis. Although additional research is needed to understand what factors are driving the uptick in EOCRC, managing body weight, improving diet quality, and mitigating psychosocial stress, may play an important role in reducing an individual’s risk of EOCRC.

Early onset colorectal cancer in Canterbury, New Zealand.

The overall incidence of colorectal cancer is decreasing in much of the world, yet the incidence in those under 50 years of age is increasing (early onset colorectal cancer (EOCRC)). The reasons for this are unclear. This study was undertaken to describe the clinical, pathological and familial characteristics of patients with EOCRC and their oncological outcomes and compare this with previously published data on late onset colorectal cancer (LOCRC). A retrospective review of all patients diagnosed with EOCRC in Canterbury between 2010 and 2017 was conducted. Data was collected on demographics, family history, treatment, and oncologic outcomes. Kaplan-Meier survival curves were calculated to assess overall survival based on disease stage. During the study period (2010-2017) there were 3340 colorectal cancers diagnosed in Canterbury, of which 201 (6%) were in patients under 50 years (range: 17-49). Of these, 87 (43.3%) were female and 125 (62.2%) were aged between 40 and 49 years. 28 (13.9%) were associated with hereditary conditions. Of the 201 patients, 139 (69.2%) had rectal or left-sided cancers. 142 (70.6%) patients presented with either stage 3 or 4 disease and the 5-year overall survival by stage was 79.1% and 14.4%, respectively. EOCRC is increasing and usually presents as distal left sided cancers, and often at an advanced stage. They do not appear to have the common risk factors of family history or inherited pre-disposition for colorectal cancer. Planning by healthcare providers for this epidemiological change is imperative in investigating symptomatic patients under 50 and optimizing early detection and prevention.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Peritoneal Metastases: A Summary of Key Clinical Trials.

The peritoneal cavity is a common site of metastatic spread from colorectal cancer (CRC). Patients with peritoneal metastases (PM) often have aggressive underlying tumor biology and poor survival. While only a minority of patients with CRC have potentially resectable disease, the high overall incidence of CRC makes management of PM a common clinical problem. In this population, cytoreductive surgery (CRS)-hyperthermic intraperitoneal chemotherapy (HIPEC) is the only effective therapy for appropriately selected patients. In this narrative review, we summarize the existing literature on CRS-HIPEC in colorectal PM. Recent prospective clinical trials have shown conflicting evidence regarding the benefit of HIPEC perfusion in addition to CRS. Current strategies to prevent PM in those at high-risk have been shown to be ineffective. Herein we will provide a framework for clinicians to understand and apply these data to treat this complex disease presentation.

Risk Factors of Young-Onset Colorectal Cancer: Analysis of a Large Population-Based Registry.

Background As the third most common type of cancer in the United States, colorectal cancer (CRC) was previously thought to be rare in young populations. Despite a decrease in the overall incidence of CRC, the rate of new cases under 50 years old has been continuously increasing. Aim The purpose of our study was to analyze risk factors of young-onset CRC. Methods Commercially available software platform, Explorys, was used to extract data from a collective healthcare database electronically. Results In this database, 13,800 young adults (age 20–50) were diagnosed with primary colorectal malignancy. Compared to subjects with a previous family history of CRC who had an odds ratio of 17.78, those diagnosed with primary malignant neoplasm of breast and inflammatory bowel disease (ulcerative colitis and Crohn's) had odds ratios of 16.94, 4.4, and 3.7 for young-onset CRC, respectively. Patients with a history of alcohol abuse, smoking, obesity, diabetes mellitus, and hyperlipidemia had higher chances of developing young-onset CRC. In addition, the odds of CRC were lower in Hispanic ethnicity in comparison to Caucasians (OR: 0.54), with no statically significant differences between Caucasian, African American, and Asian populations. Conclusion Currently, this is an expansive study investigating the risk factors for early-onset CRC. The analysis showed factors such as family and individual history of IBD to have high association with early onset. Notably, an individual history of breast malignancy was strongly associated with early-onset CRC.

Young-onset colorectal cancer: A review.

Despite the general decrease in overall incidence of colorectal cancer since the early 1990s, the incidence of colorectal cancer in patients less than 50 years old has nearly doubled. A systematic review was performed using the PubMed database (2011-2020) and Cochrane Database of Systematic Reviews (2011-2021) to identify studies (published in English) evaluating epidemiologic, clinical, hereditary, and molecular features; as well as evaluation, management, and prognosis of young-onset colorectal cancer patients. Our search yielded a total of 3401 articles, after applying our inclusion criteria. We fully reviewed 94 full-length studies. This systematic review demonstrates the increasing incidence of young-onset colorectal cancer and highlights the importance of being hypervigilant for the differential diagnosis colorectal cancer when evaluating a young adult who presents with gastrointestinal symptoms.

The incidence of young-onset colorectal cancer in Canada continues to increase

BackgroundDespite decreases in the overall incidence of colorectal cancer (CRC) in Canada, a concerning increase has been observed among younger adults in recent years. The aim of this study was to update age-specific incidence trends of CRC from 1971 to 2017 in Canada. MethodsData was obtained from the National Cancer Incidence Reporting System and the Canadian Cancer Registry. Age-specific annual percent changes in the incidence of CRC was estimated using NCI’s Joinpoint Regression Program. ResultsThe incidence of CRC among adults over age 50 has continued to decrease, while the incidence among adults under the age of 50 has continued to rise. The largest increases have occurred among 20−29 and 30−39 age groups for colon and rectal cancers, respectively. ConclusionThe incidence of CRC among young adults, particularly those under 40, continues to increase among men and women in Canada. Studies examining potential risk factors for young-onset CRC are required.

Increasing incidence of colorectal cancer among the younger population in Sweden.

BackgroundThe incidence of colorectal cancer in patients aged less than 50 years is increasing in Western countries. This population‐based study investigated the age‐ and sex‐specific incidence of colorectal cancer over time in Sweden, and characterized trends in tumour localization and stage at diagnosis.MethodsPatients diagnosed with colorectal cancer between 1970 and 2016 were identified from the Swedish Cancer Registry, and categorized by sex, age and tumour location. The incidence and average annual percentage change (AAPC) were estimated and compared between age groups.ResultsThere was an overall increase in the incidence of colorectal cancer between 1970 and 2006, but a decrease in 2006–2016 (AAPC −0·55 (95 per cent c.i. −1·02 to −0·07) per cent). The largest increase in colonic cancer was in 1995–2005 in women aged less than 50 years (AAPC 2·30 (0·09 to 4·56) per cent versus 0·04 (−1·35 to 1·44) and − 0·67 (−1·62 to 0·28) per cent in women aged 50–74 and 75 years or more respectively). Since 1990, rectal cancer increased in patients of both sexes aged below 50 years, with higher AAPC values in women (2006–2016: 2·01 (−1·46 to 5·61) per cent versus 0·20 (−2·25 to 2·71) per cent in men). Younger patients were more likely than those aged 50–74 and 75 years or more to present with stage III–IV colonic (66·2, 57·6 and 49·6 per cent respectively) and rectal (61·2, 54·3 and 51·3 per cent) cancer. From the mid 1990s, rates of proximal and distal colorectal cancer, and rectal cancer were increased in patients aged less than 50 years.ConclusionThe overall incidence of colorectal cancer in Sweden decreased in the past decade. However, in patients under 50 years of age the incidence of colorectal cancer – proximal, distal and rectal – continued to increase over time.

Colorectal cancer under the age of 50 years in U.S. Department of Veterans Affairs: Is there a role of early screening?

4072 Background: While the overall incidence of colorectal cancer (CRC) is decreasing, the rate has increased in population under 50, with higher stages at diagnosis and a greater proportion of African Americans (AA). Hence, there is an ongoing debate about the age of CRC screening. These trends have not been studied in the VA population. Methods: ICD-10 codes C18-C20 were used to identify the cases of colon and rectal cancer in National VA Cancer Cube Registry. 43,544 cases of colon cancer, 1,278 below and 42,254 above age 50, and 19,815 cases of rectal cancer, 862 below and 18,948 above age 50 were identified between 2003-17. Younger age group was defined as patients less than 50 years old. IRB approval was obtained. Results: Our data comprised > 97% of male patients. In younger group, in the 5 year periods, 2003-07, 2008-12 and 2013-17, colon cancer rate increased from 2.59% to 2.79% to 3.59%, while for rectal cancer it increased from 3.5% to 4.3% to 5.3% (p < .0001). Blacks comprise 31.6% cases of colon cancer and 27.15% cases of rectal cancer in under 50 group, compared to 18.5% and 15.9% of cases in above 50 group respectively (p < .0001). For under 50 group, 48.6% cases of colon and 42.2% cases of rectal cancer were diagnosed in stage III or IV compared to 35.7% and 34.05% cases in above 50 group respectively (p < .0001). For colon cancer, 51.87% of patients in the younger group have a < 5 year survival, worse compared to 45.05% in 50-60 group (p < .0001) and similar to 49.3% in 60-70 group (p = .08). For rectal cancer, 5 year survival showed no difference between these groups. Stage specific survival shows no difference for either colon or rectal cancer across < 50, 50-60 and 60-70 age groups. Conclusions: Rate of CRC is rising in < 50 age group with more advanced stage at diagnosis and higher proportion of African Americans. For colon cancer, < 50 group has a worse 5 year survival as compared to 50-60 age group likely due to increased proportion of patients in stage III or IV, as there is no difference in stage specific survival. For rectal cancer, the 5 year survival or stage specific survival shows no difference in < 50, 50-60 and 60-70 groups. These results add to our understanding of the trends of CRC and should be accounted for in the screening guidelines.

Risk of colorectal cancer in a population-based study 20 years after diagnosis of ulcerative colitis: results from the IBSEN study

ObjectiveThe association between ulcerative colitis (UC) and colorectal cancer (CRC) is widely accepted, although attenuated risk has been reported in recent years. Colonoscopic surveillance is recommended with intervals based on...

Photodynamic diagnosis and photodynamic therapy of colorectal cancer in vitro and in vivo.

Colorectal cancer (CRC) is a global challenge to eradicate. Early diagnosis and treatment strategies with ideal advantages, such as high tumor selectivity and negligible adverse effects, are significant, since they can result in precise diagnosis and treatment to reduce the overall incidence of CRC. The photodynamic approach for the detection and therapeutic treatment of cancer is a promising novel strategy in comparison to conventional treatments. Photodynamic diagnosis (PDD) is a diagnostic modality that involves the emission of light-induced excitation fluorescence to enhance early detection, without tumor destruction, after photosensitizer exposure to blue light. Photodynamic therapy (PDT) is a photochemistry-based approach that is rapidly progressing to solve the limitations of standard CRC treatments. PDT involves the interaction of a photosensitizer, tissue oxygen, and red light, which forms reactive oxygen species and radicals to elicit localized cancer cell death. This review discusses conventional CRC diagnostic and treatment methods, with their limitations, in comparison to the newly evolving in vitro and in vivo photo-diagnostic and treatment regimes, which have been investigated over the last several years. It also gives an overview of the integration of PDT with PDD, and utilization of specific photosensitizers for the possible early diagnosis and treatment of CRC.

Changes in colorectal cancer incidence in seven high-income countries: a population-based study

The overall incidence of colorectal cancer is decreasing in many high-income countries, yet analyses in the USA and other high-income countries such as Australia, Canada, and Norway have suggested increasing incidences among adults younger than 50 years. We aimed to examine longitudinal and generational changes in the incidence of colon and rectal cancer in seven high-income countries. We obtained data for the incidence of colon and rectal cancer from 21 population-based cancer registries in Australia, Canada, Denmark, Norway, New Zealand, Ireland, and the UK for the earliest available year until 2014. We used age-period-cohort modelling to assess trends in incidence by age group, period, and birth cohort. We stratified cases by tumour subsite according to the 10th edition of the International Classification of Diseases. Age-standardised incidences were calculated on the basis of the world standard population. An overall decline or stabilisation in the incidence of colon and rectal cancer was noted in all studied countries. In the most recent 10-year period for which data were available, however, significant increases were noted in the incidence of colon cancer in people younger than 50 years in Denmark (by 3·1%), New Zealand (2·9%), Australia (2·9%), and the UK (1·8%). Significant increases in the incidence of rectal cancer were also noted in this age group in Canada (by 3·4%), Australia (2·6%), and the UK (1·4%). Contemporaneously, in people aged 50-74 years, the incidence of colon cancer decreased significantly in Australia (by 1·6%), Canada (1·9%), and New Zealand (3·4%) and of rectal cancer in Australia (2·4%), Canada (1·2%), and the UK (1·2%). Increases in the incidence of colorectal cancer in people younger than 50 years were mainly driven by increases in distal (left) tumours of the colon. In all countries, we noted non-linear cohort effects, which were more pronounced for rectal than for colon cancer. We noted a substantial increase in the incidence of colorectal cancer in people younger than 50 years in some of the countries in this study. Future studies are needed to establish the root causes of this rising incidence to enable the development of potential preventive and early-detection strategies. Canadian Partnership Against Cancer, Cancer Council Victoria, Cancer Institute New South Wales, Cancer Research UK, Danish Cancer Society, National Cancer Registry Ireland, the Cancer Society of New Zealand, NHS England, Norwegian Cancer Society, Public Health Agency Northern Ireland, Scottish Government, Western Australia Department of Health, and Wales Cancer Network.

Is increased colorectal screening effective in preventing distant disease?

BackgroundScreening in the average risk population for colorectal cancer (CRC) is expected to reduce the incidence of distant (i.e., metastatic) CRCs at least as much as less advanced CRCs. Indeed, since 2000, during which time colonoscopy became widely used as a screening tool, the overall incidence of CRC has been reduced by 29%.ObjectiveThe purpose of the current study was to determine whether the reduction of incidence rates is the same for all stages of disease.MethodsWe evaluated incidence data from the Surveillance, Epidemiology, and End Results (SEER) program from 2000–2014 for Localized, Regional, and Distant disease. Joinpoint models were compared to assess parallelism of trends. Data were stratified by race, age, tumor location, and sex to determine whether these subgroupings could explain overall trends.ResultsInconsistent with the expectations of a successful screening program, the reduction in incidence rates of distant CRCs from 2000–2014 has been slower than the reductions in incidence rates of both regional and localized CRCs. This trend is evident even when the data are stratified by age at diagnosis, sex, race, or tumor location.ConclusionsThe slower decrease in the incidence rate of distant disease is not consistent with a screening effect, that is, CRC screening may not be effective in preventing many distant CRCs. As a consequence, distant CRCs represent an increasing fraction of all CRCs, accounting for 21% of all CRCs in 2014. The analysis indicates that inadequate screening does not explain the slower decrease in incidence of distant CRCs. Consequently, we suggest that a subtype of CRC exists that advances rapidly, evading detection because screening intervals are too long to prevent it. Microsatellite unstable tumors represent a known subtype that advances more rapidly, and we suggest that another rapidly advancing subtype very likely exists that is microsatellite stable.

Clinical and molecular characteristics of younger versus older patients with colorectal cancer.

630 Background: Although overall incidence of colorectal cancer is declining, the incidence for young patients (age < 50) with colon cancer is increasing. Reasons for this rise are unclear. Understanding clinical and molecular differences between younger and older cohorts can help guide both patient education strategies and future research into the mechanisms of this phenomenon. Methods: A retrospective analysis of patients diagnosed with colon cancer between 2008 and 2015 who underwent molecular tumor profiling via next-gen sequencing of 26 commonly mutated genes at the University of Colorado. Data collected by chart review includes demographic, pathologic, treatment course, and outcomes. Age group cutoffs for data analysis were set at < 50, 50-65, and > 65 based on screening guidelines and average age of diagnosis Results: We evaluated a total of 242 patients, stage I (n = 1), stage II (n = 65), stage III (n = 68), stage IV (n = 105). Mean age was 59.5 (range 27 to 89). A higher percentage of younger patients were non-smokers (77% of youngest cohort vs 46% of oldest cohort, p < 0.001) and had a non-significant trend towards male gender (youngest cohort 63.8% male, oldest cohort 43.4% male, p = 0.065). Younger patients had similar body mass index (BMI) compared to older patients (BMI 27 vs 25.7, p = 0.35). Younger patients had higher rates of rectal cancer (42% vs 21%, p = 0.01) and lower rates of proximal/right sided colon cancer (20% vs 46.5%, p = 0.014). Younger patients also had lower rates of MSI-H tumors (8% vs 14%, p = 0.01). Finally, younger patients had significantly lower rates of APC (43.1% vs 69.3%, p = 0.009) and BRAF (3.5% vs 19.7%, p = 0.004) mutations. Conclusions: Younger patients ( < 50 years old) with colorectal cancer had lower rates of tobacco use and no difference in obesity rates compared to older patients. In addition, although APC and BRAF mutations were lower in younger patients, there were no mutations that were more prevalent in the young cohort. Therefore, further research into lifestyle factors (specific diet/exercise patterns) or alternative molecular mechanisms are needed.

Clinicopathologic Features of Young Onset Colorectal Cancer Patients: Results From a Large Cohort at a Single Cancer Center

Introduction: Whereas the overall incidence of colorectal cancer (CRC) in the United States (US) is decreasing, its incidence in young adults (<50 years old) is increasing. The cause of this remains unclear, and the characteristics of patients with young onset CRC have not been fully elucidated. The aim of this study is to describe the demographics, clinical and pathologic features of patients with young onset CRC. Methods: We performed a retrospective review of all patients with CRC diagnosed between ages 20 and 49 years evaluated at Memorial Sloan Kettering Cancer Center from January 2004 to April 2015. We excluded those with a history of a hereditary CRC syndrome, inflammatory bowel disease, or prior diagnosis of CRC. Patient demographics, presenting symptoms, smoking history, family history of cancer, medical and surgical history, tumor characteristics, and pathology were obtained from the electronic medical record. Baseline characteristics were compared to those found in a nationally representative cohort of cancer-free individuals age 20 to 49 in the US National Health and Nutrition Examination Survey (NHANES). Results: We identified 3,238 young onset CRC patients. Median age of CRC diagnosis was 44; 52% were male (Table 1). Compared with the NHANES population, patients had a lower body mass index (BMI), a higher rate of hypertension and diabetes, and were more likely to have never smoked (Figure 1). The most common presenting symptoms were rectal bleeding (49%), followed by abdominal pain/bloating (33%) and change in bowel habits (25%) (Figure 2). The majority of patients presented with left sided cancers (69%), at late stage disease (65% at stages 3 or 4) (Table 2), and had no family history of CRC (68%) (Table 1).Figure: Comparison of clinical variables for MSK patient population vs. NHANES cancer-free population <50 years old.Figure: Percentage of patients who presented with a given symptom ABBREVIATIONS: BRBPR (bright red blood per rectum); FOBT+ (Fecal occult blood test positive).Table: Table. Demographic Characteristics of Patients ( N =3,238)Table: Table. Cancer Characteristics of MSK Patients Overall and by Age Decade ( N , 3,238)Conclusion: To date, this is the largest single center study describing the demographics, clinical and pathologic features of young onset CRC. Most patients presented with symptoms of rectal bleeding or abdominal pain, left sided cancers, later stage disease and had no family history of CRC. Compared to a US nationally representative population, these patients had a greater prevalence of hypertension and diabetes. More data are needed to better understand risk factors for young onset CRC, and to help identify high-risk patient populations who may benefit from earlier screening.

Disparities in incidence of early- and late-onset colorectal cancer between Hispanics and Whites: A 10-year SEER database study

BackgroundRacial disparities in incidence of colorectal cancer (CRC) exist. In Hispanics, CRC was the second most commonly diagnosed cancer in 2012. MethodsWe abstracted the national estimates for Hispanics/Whites with CRC using the SEER database between 2000 and 2010. Trends in incidence, mortality, gender and stage of disease were analyzed for early-onset (age<50; EO - young) and late-onset (age>50; LO - old) cases. ResultsThe overall incidence of CRC increased by 48% in Hispanics. 38% increase in incidence of LO CRC and 80% increase in incidence of EO CRC was seen in this ethnic group. Hispanics and Whites showed higher percentage of distant tumors for both age groups. There was no deviation in overall trend between males and females. ConclusionsAlthough there is an overall decrease in incidence of CRC in Whites increase was seen in Hispanics. While incidence of EO CRC is increasing in both races, LO CRC incidence is increasing in Hispanics not in Whites. This data suggest that disparities in incidence of EO and LO CRC exist between Hispanics and Whites.

Colorectal cancer anatomic distribution patterns remain the same after sessile serrated adenoma/polyp considered cancer precursor: a 9-year comparison study from community-based endoscopy centers.

The overall incidence of colorectal cancer (CRC) in the United States has steadily decreased. However, the incidence of right-sided CRC remains unchanged for the past two decades. The serrated neoplastic pathway (sessile serrated adenoma/polyp, SSA/P) has been considered an important pathway of colorectal carcinogenesis, especially in the right-sided CRC. The aim of this study was to compare CRC anatomic distribution patterns in a 9-year interval in the general population before and after SSA/P was recognized and treated as a CRC precursor. The Miraca Life Sciences (MLS) pathology database was queried for all primary CRCs diagnosed between 8/3/2000 to 12/31/2005 (control group) and 1/1/2014 to 12/31/2014 (current group). Patients' demographics, clinical information, and pathology reports were collected and analyzed. A total of 5,602 patients with 5,685 CRCs were identified, of which 2,728 patients with 2,765 CRCs in current group and 2,874 patients with 2,920 CRCs in control group. Overall, there were no statistical differences in the current group in regards to the anatomical distribution patterns of CRCs in the proximal, right-sided, distal, and left-sided colon or genders compared with the control group (all P>0.05). Among the current group, there were 33 (1.2%) patients with 38 (1.4%) CRCs arising in SSA/Ps [serrated carcinomas (SCAs)], of which 33 (86.8%) were in the right-sided colon and 5 (13.2%) in the left-sided colon. Twenty-three (69.7%) SCA patients were female with significant advanced age than male (76.4 vs. 69.6, P=0.023). The overall current CRC anatomic distribution patterns after SSA/Ps managed as CRC precursor remain the same in the patients' population from the community-based endoscopy centers in the U.S. It is suggested that the current SSA/P management might need to be further modified.

Colorectal cancer incidence in 5 Asian countries by subsite: An analysis of Cancer Incidence in Five Continents (1998–2007)

Colorectal cancer is the fourth most common cancer in Asia. However, the trends in colorectal cancer incidence by subsite have not been analyzed across Asian countries. We used the most recent, high quality data from 6 cancer registries for two 5-year periods, 1998–2002 and 2003–2007, from Cancer Incidence in Five Continents to estimate colorectal cancer incidence by subsite in 5 Asian countries. Cases with overlapping lesions or otherwise unspecified colon cancer were re-distributed as proximal or distal colon cancer. Age-standardized incidence rates (ASRs) per 100,000 population and incidence rate ratios from 1998 to 2002 to 2003–2007 were calculated for each subsite. For 2003–2007, men in Miyagi, Japan, had the highest ASR for cancer in the proximal colon, distal colon and rectum. Men of Jewish ancestry in Israel had a high ASR for proximal and distal colon cancer, but the lowest ASR for rectal cancer. The proportion of rectal cancer was highest among Korean men (51.39%) and lowest among Israeli women (26.6%). From 1998–2002 to 2003–2007, rectal cancer incidence did not significantly change in most registries, except for men in Miyagi, Japan, and both sexes in Korea. However, during the same period cancer incidence in the proximal and distal colon increased in most registries. In conclusion, there was substantial variation in subsite distributions of colorectal cancer in Asian registries and increases in overall incidence of colorectal cancer could be attributed to increases in colon cancer.

The 2011-2016 Incidence of Colorectal Cancer in Individuals Under 40 Years of Age: A Retrospective Analysis from the Explorys Database: 2016 ACG Presidential Poster Award

Introduction: Recent literature has demonstrated an increasing incidence of colorectal cancer (CRC) in younger patients. The aim of the study was to investigate the 2011-2016 incidence of CRC in individuals under 40 years of age using a large population-based database. Methods: We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of electronic health record (EHR) data from 23 major integrated U.S. healthcare systems from June 2011 to June 2016. We identified an aggregated patient cohort of eligible patients under 40 years of age with first-ever diagnosis of “Primary malignant neoplasm of the colon and/or Primary malignant neoplasm of the rectum”, based on Systemized Nomenclature Of Medicine - Clinical Terms (SNOMED-CT). Tumors were classifi ed into right-sided cancers (from the cecum to and including the splenic flexure), left-sided cancers (located in the descending and the sigmoid colon), and rectal cancers. The Pearson Chi-square test was used to compare the data. Results: Of the 49,029,080 individuals in the database, we identified 1,790 patients under the age of 40 years who were diagnosed with CRC. The overall incidence of CRC in individuals under 40 years of age was 13.1/100,000 persons (Figure 1). The age-based incidence of CRC under 40 years of age showed an exponential increase from younger to older age intervals (Figure 2). The incidence of CRC was higher in Asians as compared to African-Americans and Caucasians (OR=1.36; 95% CI=1.09-1.71, p=0.006). Males were also more likely to develop CRC when compared to females (OR=1.15, 95% CI= 1.05-1.26, p=0.002). Among the anatomical sub-site location of incident CRC cases under 40 years of age, the majority of cases were right-sided cancers (43.5%), followed by left-sided cancers (31.5%) and rectal cancers (25%). While Caucasians and African-Americans were more likely to present with right-sided cancer (p=0.008), Asians were more likely to present with rectal cancer (p=0.0004).Figure 1Figure 2Conclusion: In this large population-based study, the estimated five-year incidence of CRC in individuals under 40 years of age in the US is 13.1/100,000 persons with predominance in Asians and males. The majority of incident CRC cases were right-sided. Further studies are needed to understand the evolving epidemiology of CRC in the younger population.

Abstract 141: Gene expression profile differences between early- and late-onset colorectal adenocarcinoma

Abstract Introduction: Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer related deaths in the US. The overall incidence of CRC in the US has decreased over the past three decades, yet recent literature indicates increase in incidence among individuals younger than 50. These early-onset CRC tumors (EO) tend to be more aggressive and advanced at initial diagnosis. As the etiology of EO CRC is not understood yet, the aim of this study was to elucidate gene expression profiling in EO CRC and show its molecular uniqueness compared to late-onset (LO) CRC. Methods: Two cohorts of patients with sporadic EO CRC (age under 50) and LO CRC (age over 65) tumors were identified. Tumors and their matching non-involved tissue samples with equal representation of colon and rectal neoplasms from twelve EO patients and twelve LO patients were obtained. Patients with Lynch syndrome, familial adenomatous polyposis and inflammatory bowel disease were excluded. De-paraffinized tissues were macro-dissected from FFPE sections, RNA isolated and used for nanoString nCounter PanCancer Pathways Panel gene expression analysis to quantify transcript levels of 770 genes representing 13 canonical cancer pathways. Statistical analysis was performed using the Gene Expression R-script module within the nCounter software v2.6. A gene was considered to be above background if the average count for the target gene was greater than the average counts for the eight negative control genes and if the P value of the t-test was less than 0.05. Results: We analyzed a total of twenty four tumor samples, six EO and six LO colon tumors and six EO and six LO rectal tumors. Their expression profiles were then compared to their matching non-involved tissues in order to identify genes that are unique to colon and rectal neoplasm, respectively. Out of 770 PanCancer Panel pathway genes assayed, 98 genes were uniquely expressed in EO colon tumors with 73 genes being up- and 25 down-regulated with a fold change higher than two. 77 genes were uniquely expressed in EO rectal tumors, with 57 of them up-regulated and 20 down-regulated. Further statistical analysis revealed that, from 265 genes differentially expressed specifically in EO colon tumors, changes in expression of 147 genes were statistically significant (p&amp;lt;0.05). Similarly, from 275 genes differentially expressed in EO rectal tumors, 82 showed statistically significant alterations in expression. Conclusions: Results of this study suggest EO CRC as a distinct molecular subtype which is characterized by unique molecular events compared to LO disease. Further studies using larger cohorts of patients are needed to validate these findings. Such studies might offer the possibilities of coming up with novel molecular markers to enhance newer, faster and noninvasive detection modalities for young patients with CRC tumors. Citation Format: Valentine N. Nfonsam, Jana Jandova. Gene expression profile differences between early- and late-onset colorectal adenocarcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 141.